Effect of tachykinin receptor antagonists in experimental neuropathic pain

The intrathecal effect of 0.1 to 10 mu g of RP-67,580 (3aR,7aR)-7,7-dipheny l-2[1-imino-2(2-methoxyphenyl)-ethyl]perhydroisoindol-4-onehydro chloride, CP-96,345 (2S,3S)-cis-(2(diphenylmethyl)-N-[(2-methoxyphenyl) methyl]-1-aza bicyclo[2.2.2]octan-3-amine), SR-140,333 (S)-(1-{2-[3-(3,4-dichlorophenyl)- 1-(3-isopropoxyphenylactyl)piperidin-3-yl]ethyl}-4-phenyl-1-azonia-bicyclo[ 2.2.2.]-octane, chloride), all neurokinin (NK)(1)-receptor antagonists, SR- 48,968 (S)-N-methyl-N [4-(4-acetylamino-4-[phenylpiperidino)-2-(3,4-dichlor ophenyl)-butyl]benzamide, a tachykinin NK2 receptor antagonist and SR-142,8 01 (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4 -phenylpiperidin-4-yl)-methyl acetamide, a tachykinin NK3 receptor antagoni st, and of their respective inactive enantiomers on thresholds of vocalizat ion due to a mechanical stimulus in mononeuropathic (sciatic nerve ligature ) and diabetic rats, was examined. The tachykinin NK1 and the NK2 receptor antagonists were antinociceptive in both models, with a higher effect of th e former in diabetic rats. The tachykinin NK3 receptor antagonist was weakl y effective in diabetic rats only. This indicates a differential involvemen t of the tachykinins according to the model of neuropathic pain, suggesting a potential role for tachykinin receptor antagonists in the treatment of n europathic pain. (C) 1998 Elsevier Science B.V. All rights reserved.